Mass spectrometer for simulataneous detection of reflected and direct ions

ABSTRACT

Techniques for simultaneously detecting direct and reflected ions in a time-of-flight tube ( 120 ) and a source ( 110 ) for generating an ion beam of ions of a sample and introducing the ion beam into a first portion of the flight tube. A reflector ( 126 ) reflects ions from the ion beam in a second portion of the flight tube. A plate ( 140 ) substantially perpendicular to an axis of the ion beam is located between the first portion of the flight tube and the second portion of the flight tube. The plate has a hole through which some ions in the ion beam may pass from the first portion to the second portion of the flight tube. Each of two opposite faces of the plate includes a set of one or more ion detectors ( 140 ). The technique allows rapid, reliable detection of complex agents in a small number of samples.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit of Provisional Application60/323,563 filed Sep. 20, 2001, the entire contents of which are herebyincorporated by reference as if fully set forth herein, under 35 U.S.C.§119(e).

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to mass spectrometry of sampleswith complex molecules, and more particularly to mass spectrometry thatsimultaneously detects direct (“linear”) and reflected time-of-flightmass spectra.

[0004] 2. Description of the Related Art

[0005] The past approaches described in this section could be pursued,but are not necessarily approaches that have been previously conceivedor pursued. Therefore, unless otherwise indicated herein, the approachesdescribed in this section are not to be considered prior art to theclaims in this application merely due to the presence of theseapproaches in this background section.

[0006] Populated locations are susceptible to natural and artificialinfestations of biological agents that are harmful to human health.Early detection of such infestations allows rapid evacuation of suchlocations and provides one line of defense. Rapid treatment of exposedindividuals provides a second line of defense. Correct treatment oftendepends on rapid, correct identification of the harmful agent.

[0007] One method commonly used to detect and identify biological agentsis mass spectrometry, in which a distinctive distribution of molecularweights is associated with each of several biological agents of interestin protecting public health.

[0008] In mass spectrometry, a sample of material is ionized, whichchanges molecules in the sample to ions (molecules with a net electricalcharge). For example, a laser can be used to remove electrons from themolecules, leaving positive ions. The ions are accelerated in a sourceregion using an electric field. For a given electrical voltage used toaccelerate the ions, the less massive ions are accelerated to fasterspeeds than are the more massive ions. Outside the source region, in aregion called a “drift region,” each ion travels at a characteristicspeed inversely related to its mass. Therefore, the times of flight forthe ions to travel from the source region to a detector are related tothe masses of the ions. To reduce collisions with air molecules, thesource region and drift region are in a vacuum that can be readilyproduced in a vacuum chamber or that is ambient outside the earth'satmosphere.

[0009] Because some of the molecules of interest are rather large, adifference of a few atomic mass units between two molecules, related toa difference in chemical and biological properties, is associated with arelatively small difference in mass and therefore a relatively smalldifference in speed. To distinguish two molecules that are close in massand speed, a rather long path for the ions is desirable to increase thedifference in time of flight.

[0010] Problems arise when the path length is increased. For example,paths of the ions tend to diverge in the drift region; and, thus, moreions miss the detector, decreasing the signal at the detector. To reducedivergence, the ions are focused into an ion beam during theacceleration stage. Focusing the ions into an ion beam reduces thenumber of ions that miss the detector.

[0011] Furthermore, increasing the path length involves increasing thelength of the drift region, which increases the size of the massspectrometer. A larger mass spectrometer is a disadvantage and can causethe mass spectrometer to be too large for some applications. Forexample, a mass spectrometer that is too large may be unsuitable for aportable unit, or unsuitable for deployment in aircraft, air ducts, andother useful places. The problems are exacerbated if the ion detector isalso made larger to compensate for the greater divergence over thelonger paths.

[0012] In another approach, the path length is essentially doubledwithout appreciably increasing the size of the mass spectrometer byreflecting the ion beam in a reflecting electric field. The reflectingelectric field is tuned to the accelerating field in the source regionso that the ions reverse direction after traversing the length of thereflecting region and before striking the end wall of the spectrometer.In conventional reflected time-of-flight mass spectrometers, adirectional detector is placed close to the source but facing away fromthe source. A hole in the detector allows most of the ions in the ionbeam from the source to pass through the detector into a reflectionportion of the spectrometer. When the ions in the beam are reflected tomove back toward the source, many of the ions strike the detector.

[0013] A problem with the reflected time-of-flight mass spectrometer isthat some very large molecules are too fragile to be decelerated to zeroand accelerated into the reverse direction without breaking apart intotwo or more fragments. For example, molecules with masses of about10,000 atomic mass units (amu) or higher tend to fragment in a reflectedtime-of-flight mass spectrometer (an atomic mass unit is about the massof a proton). One or more of the fragments may be uncharged. Anuncharged fragment most likely strikes a wall of the mass spectrometerwithout ever impinging on the detector and might not be detected even ifit does strike the detector. The mass of the fragment becomes lost tothe detector. Lighter fragments that retain a charge will be reversedtoo quickly and strike the detector after a time of flight associatedwith lower mass molecules.

[0014] Another problem with a reflected time-of-flight mass spectrometeris that an incentive to make the detector hole large enough to pass mostof the ion beam conflicts with a motivation to make the detector hole assmall as possible to detect most of the reflected ions. As a result, thehole is often so small that a signfficant number of ions are lost thatstrike the back of the detector and never enter the reflection region.This decreases the signal at the detector.

[0015] To be useful as a line of defense in populated areas, the massspectrometer should detect harrful biological agents with few, smallsamples that can be filtered from the air or water serving the populatedareas. False alarms, caused by detections based on noisy data, should beavoided. A system that repeatedly fires a warning when no danger isactually present is more likely to be ignored when a real threat isdetected. To reduce false alarms multiple measurements should be madethat verify the existence of the mass distributions upon which detectionis based. Well known statistical tests can be performed to generateconfidence limits on the detections. Statistical confidence is achievedonly after several samples are independently measured.

[0016] A problem with conventional mass spectrometer is that so muchtime is consumed in making several independent measurements that manymore people are exposed to the agent before an alarm can be fired. Thisdiminishes the conventional mass spectrometer's effectiveness on oneline of defense. For example, to prepare one sample or set of samplesfor introduction to the mass spectrometer, to introduce the set ofsamples, to evacuate the air from the vacuum chamber and to remove thespent set of samples can take several minutes. To obtain measurementsfrom even two sets of samples doubles that time and increases theexposure of the population to the biological agent.

[0017] Furthermore, it can be difficult to obtain enough independentmeasurements when sample amount is scarce. It may be difficult to obtaina sample of the biological agent, so that any sample obtained isprecious. There may not be sufficient sample to make two independentmeasurements.

[0018] In one approach that may be pursued, a second detector may beplaced in the vacuum chamber of a reflected time-of-flight massspectrometer on a side farthest from the source. Then, before or after areflected time-of-flight measurement, the reflecting electric field canbe turned off, and a direct time-of-flight measurement can be made.However, this approach still loses signal from ions that miss the holethrough the plate for the reflected ion detections, and consumes moresample and more time than are used during the reflected time-of-flightmeasurement alone.

[0019] Based on the foregoing there is a clear need for a portable massspectrometer that can make reliable detections of biological agents,having reduced false-alarm rate, with few samples of small size in ashort time. In particular, there is a need for a mass spectrometer thatcan simultaneously measure direct and reflected time-of-flight massdistributions.

SUMMARY OF THE INVENTION

[0020] According to one aspect of the invention, an apparatus forsimultaneously detecting direct and reflected ions in a massspectrometer includes a flight tube, and a source for generating a beamof ions from a sample. The ion source introduces the ion beam into afirst portion of the flight tube. The apparatus includes a reflector forreflecting ions from the ion beam in a second portion of the flighttube. The apparatus also includes a mounting plate substantiallyperpendicular to an axis of the ion beam. The plate is installed betweenthe first portion of the flight tube and the second portion of theflight tube. The mounting plate has a hole through which some ions inthe ion beam may pass from the first portion to the second portion ofthe flight tube. Each of two opposite faces of the mounting plateincludes a set of one or more ion detectors.

[0021] According to another aspect of the invention, a method offabricating an apparatus for simultaneously detecting direct andreflected ions in a mass spectrometer includes installing, onto a flighttube, a source for generating an ion beam of ions of a sample. Thesource introduces the ion beam into a first portion of the flight tube.A reflector is also installed in the flight tube. The reflector reflectsions from the ion beam in a second portion of the flight tube. Amounting plate is installed in the flight tube substantiallyperpendicular to an axis of the ion beam between the first portion ofthe flight tube and the second portion of the flight tube. The mountingplate has a hole through which some ions in the ion beam may pass fromthe first portion to the second portion of the flight tube. Each of twoopposite faces of the mounting plate includes a set of one or more iondetectors.

[0022] In another aspect of the invention, a method for simultaneouslydetecting direct and reflected ions in a mass spectrometer includesforming an ion beam from a sample in a source of ions. A first signalindicating a number of first ions from the ion beam is generated. Thefirst ions strike a first face of a plate directed toward the source ofions. A second signal indicating a number of second ions from the sameion beam is also generated. The second ions strike a second face of theplate. The second face is directed away from the source of ions anddirected toward the second ions that pass through a hole in the plateand that are reflected in a reflecting electric field. A directtime-of-flight mass distribution is determined based on the firstsignal; and a reflected time-of-flight mass distribution is determinedbased on the second signal. The reflected time-of-flight massdistribution is independent of the direct time-of-flight massdistribution since different ions are actually detected.

[0023] In another aspect of the invention, techniques for determiningwhether a particular agent is present in a sample include receiving afirst signal. The first signal indicates a number of first ions from anion beam generated from the sample in a source. The first ions strike afirst face of a plate; the first face is directed toward the source ofions. A second signal indicating a number of second ions from the sameion beam is also received. The second ions strike a second face of theplate; the second face is directed away from the source of ions anddirected toward the second ions that pass through a hole in the plateand that are reflected in a reflecting electric field. A directtime-of-flight mass distribution is determined based on the firstsignal. A reflected time-of-flight mass distribution is determined basedon the second signal. It is determined whether the particular agent ispresent in the sample based, at least in part, on the directtime-of-flight mass distribution and the reflected time-of-flight massdistribution.

[0024] The plate with ion detectors on both opposite faces allows directtime-of-flight measurements on the face directed toward the source andreflected time-of-flight measurements on the face directed away from thesource, from different ions in the same ion beam from the same source.By simultaneously obtaining a measurement of the direct time-of-flightmass distribution that is independent of a measurement of the reflectedtime-of-flight mass distribution, two independent measurements are madeof the same small sample. This decreases the false alarm rate overconventional mass spectrometers when samples are in limited supply. Inaddition, total signal is increased, because ions that strike the plateoutside the hole to the second portion, which are lost to the reflectedmeasurement, are detected in the direct time-of-flight measurement. Inaddition, because the measurements are simultaneous (obtained withoutrepeating the sample preparation, ionization, and acceleration,detection, and removal of the sample), the independent measurementsneeded are obtained in less time than in other approaches. Furthermore,measurements of the direct time-of-flight preserve detections of massdistributions from the larger molecules that fragment in reflectedtime-of-flight configurations.

BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The present invention is illustrated by way of example, and notby way of limitation, in the figures of the accompanying drawings and inwhich like reference numerals refer to similar elements and in which:

[0026]FIG. 1A is a block diagram that illustrates a mass spectrometerthat simultaneously measures direct and reflected time-of-flight massdistributions according to an embodiment;

[0027]FIG. 1B is a block diagram that illustrates a mounting plate withion detectors on both faces, according to an embodiment;

[0028]FIG. 2A is a graph of an example mass distribution for direct(“linear”) time-of-flight, according to an embodiment;

[0029]FIG. 2B is a graph of an example mass distribution for reflectedtime-of-flight, according to an embodiment;

[0030]FIG. 3 is a flow chart that illustrates at a high level a methodfor determining an agent in a mass spectrometer, according to anembodiment; and

[0031]FIG. 4 is a block diagram that illustrates a computer system uponwhich an embodiment of the invention may be implemented.

DETAILED DESCRIPTION

[0032] A method and apparatus for simultaneously detecting direct andreflected ions in a mass spectrometer is described. In the followingdescription, for the purposes of explanation, numerous specific detailsare set forth in order to provide a thorough understanding of thepresent invention. It will be apparent, however, to one skilled in theart that the present invention may be practiced without these specificdetails. In other instances, well-known structures and devices are shownin block diagram form in order to avoid unnecessarily obscuring thepresent invention.

[0033] 1. Structural and Functional Overview

[0034]FIG. 1A is a block diagram that illustrates a mass spectrometer100 that simultaneously measures direct and reflected time-of-flightmass distributions according to an embodiment. A mass spectrometerincludes a flight tube12O, which is housed in a vacuum chamber. Inembodiments used outside Earth's atmosphere, the vacuum chamber may beomitted. The flight tube includes a source region portion 110, a driftregion portion 122, and a reflector region portion 124. A reflector 126in the reflector region portion 124 causes ions in an ion beam toreverse direction to double the path length and the time of flight inthe reflector region portion 124 of the flight tube 120.

[0035] Between the drift region portion 122 and the reflector regionportion 124 is a dual-sided channelplate detector 140 that separates thetwo portions. In some embodiments, the detector 140 is located betweenthe two portions but does not separate the two portions. The dual-sidedchannelplate detector has microchannel plate ion detectors on each oftwo sides, or “faces” of the detector. One face is directed toward thesource region portion 110 and the drift region portion 122; the oppositeface is directed toward the reflection region portion 124. Thedual-sided channelplate detector 140 is described in more detail belowwith reference to FIG. 1B. In other embodiments, another detector withion detectors on two opposite faces is used.

[0036] A sample in the source region portion 110 is ionized, and theions are accelerated and focused into an ion beam. In some embodiments,the sample is ionized by shining a laser on the sample in the sourceregion portion 110. In the drift region portion 122, the ion beam 102diverges. Some ions in the diverging ion beam 102 strike the face of thedetector 140 directed toward the source region portion 110 and the driftregion portion 122. These ions are detected in the microchannel platedetectors on that face of the detector 140 and are used to determine adirect (“linear”) time-of-flight mass distribution.

[0037] Some ions in the diverging ion beam 102 pass through a hole inthe detector 140 into the reflector region portion 124. An electricfield established by reflector 126 reverses the direction of travel ofthese ions to form a reflecting ion beam 104. Ions from the reflectingion beam 104 strike the face of the detector 140 directed toward thereflector region portion 124. These ions are detected in themicrochannel plate detectors on this face of the detector 140, and areused to determine a reflected time-of-flight mass distribution.

[0038] The linear and reflected mass distributions provide independentobservations of the mass distribution obtained from the sample in sourceregion portion 110. Different individuals of essentially the same typesof ions contribute to the measurements obtained at each plate. A samplecomponent whose characteristic mass peaks are found in bothdistributions is more likely to be actually present in the sample thento be a false alarm caused by noise or instrument error. Even a small,precious sample ionized in source region portion 110 yields at least twoindependent measurements of mass distributions.

[0039] Although the illustrated embodiment employs microchannel platedetectors on each face of detector 140, in other embodiments other iondetectors are employed. Any center-hole ion detector known in the art atthe time the mass spectrometer is constructed may be used.

[0040] In the illustrated embodiment, the vertical lines in thereflector region portion 124 represent conductors that are part ofreflector 126 in a wall of the reflector region portion 124 of flighttube 120. These conductors are each set at a different voltage to form avoltage gradient in the reflector region. In other embodiments, otherreflectors may be used. Any reflector known in the art at the time themass spectrometer is constructed may be used.

[0041] 2. Dual-Sided Channelplate Detector

[0042]FIG. 1B is a block diagram that illustrates a detector 140 made upof a mounting plate with ion detectors on both faces, according to anembodiment.

[0043] The detector 140 includes a plate shaped structural member 146configured for attachment to the flight tube 120. In the illustratedembodiment, the structural member 146 includes an attachment element 149configured to attach to a drift region portion 122 of the flight tube120 and to attach to the reflector region portion 124 of the flighttube. In other embodiments, the structural member is attached to a mountinside the flight tube 120 in any manner known at the time the massspectrometer is constructed. In one embodiment, the structural member146 is disc shaped in the plane perpendicular to the drawing of FIG. 1B;in other embodiments, the structural member has other shapes, such as arectangular shape. In some embodiments, the structural member 146 fillsa space between the drift region portion 122 and the reflector regionportion 124 of the flight tube 120, when assembled; in otherembodiments, the structural member 146 does not fill that space.

[0044] The structural member 146 includes a center hole 148 that allowssome ions of the diverging ion beam 102 to pass into the reflectorregion portion 124. In the illustrated embodiment, the hole 148 issubstantially centered in the structural member; in some otherembodiments the hole may be located at any position on the structuralmember. In some embodiments in which the structural member does not fillthe space between the drift region portion 122 and the reflector regionportion 124, ions can pass into the reflector region portion 124 outsidethe structural member 146 and the “hole” is considered part of the plateoutside the structural member 146. A hole disposed close to the centerof the detector 140 is preferred because more diverging ions andreflected ions strike the detector and provide additional signal whenthe hole that passes ions into the reflector region portion 124 is closeto the center of the detector and aligned with a center of a focused ionbeam.

[0045] The detector 140 includes two faces 141 a, 141 b with one or moreion detectors on each face. In the illustrated embodiment, each faceincludes a microchannel detectors. (A grid 143 is a fine metallic meshused to precisely define the boundaries between different electricfields. The two faces 141 a, 141 b are termed chevron microchannelplatedetector faces (or dual-sided channelplate detector faces). In otherembodiments, other ion detectors are employed on each face 141 a, 141 b.One face 141 a is directed toward the source region portion 110 and thedrift region portion 122 of flight tube 120. The opposite face 141 b isdirected toward the reflector region portion 124 of flight tube 120. Inthe illustrated embodiment, a gap is formed between the faces 141 a, 141b and portions of the structural member 146. In other embodiments theopposite faces with detectors are flush with the structural member 146.In the illustrated embodiment, the faces 141 a, 141 b do not extendoutside the perimeter of the structural member in the planeperpendicular to the drawing of FIG. 1B; in other embodiments, theopposite faces with detectors may extend outside that perimeter. Inother embodiments, grid 143 is eliminated from the detector mountaltogether.

[0046] The detector 140 includes an anode to collect electrons emittedfrom the rear of the channelplates. In the illustrated embodiment dualpin anodes 145 a, 145 b are employed. In other embodiments, other anodesmay be used, such as annular shaped anodes concentric with the faces 141a, 141 b. Ions (positive or negative ions depending on the analyzerconfiguration) from an ion beam strike the surface of each detector fromwhich secondary electrons are subsequently ejected. This electron signalis amplified as the electrons cascade along the inner surfaces ofmicro-channels within the detector. A large number of electrons emergefrom the rear of the detector for each ion that strikes the frontsurface of the detector, resulting in a large gain in electricalcurrent. For example, a gain of approximately 10⁶ can be achieved.

[0047] The detector 140 includes two output terminals, each forproviding a signal related to the number of ions. For example, thecurrents at the anodes 145 a, 145 b are converted to voltage signals.These voltage signals at the two terminals are related to the number ofions that strike the two opposite faces. A linear output terminal 142carries a signal related to the number of ions that strike face 141 adirected toward the source region portion 110 and drift region portion122. A reflected output terminal 144 carries a signal related to thenumber of ions that strike face 141 b directed toward the reflectorregion portion 124.

[0048] 3. Example Data from Dual-Sided Channelplate Detector

[0049]FIG. 2A is a graph of an example linear spectrum 240 that shows amass distribution for direct (“linear”) time-of-flight, according to anembodiment. FIG. 2A is based on time-of-flight measurements for ionsdetected on face 141 a of the detector 140 depicted in FIG. 1B. FIG. 2Bis a graph of an example reflector spectrum 250 that shows a massdistribution for reflected time-of-flight, according to an embodiment.FIG. 2B is based on time-of-flight measurements for ions detected onface 141 b of the detector 140 depicted in FIG. 1B.

[0050] The graphs of FIG. 2A, FIG. 2B plot voltage amplitude on voltageaxes 220 a, 220 b against mass on mass axes 210 a, 210 b, respectively.Voltage amplitude is provided by the signal on the linear outputterminal 142 and the reflected output terminal 144, respectively, and isrelated to the number of ions striking the microchannel plate detectorson faces 141 a, 141 b, respectively. Mass, measured in atomic mass units(amu), is derived from time-of-flight measurements as is well known inthe art. The path lengths from the source region portion 110 to thedetectors are known for each of faces 141 a, 141 b. The path length toeach face 141 a, 141 b divided by the measured time-of-flight indicatesthe average speed of the ions. The energy provided by the source field(in electron volts) divided by the square of the speed is proportionalto the mass (or said another way—an ion's time-of-flight is proportionalthe square root of its mass).

[0051] It is noted that the path length to the first face 141 a, is muchshorter than the path length to the second face 141 b. Therefore amolecule of a given mass, say 6000 amu, arrives at the first face 141 amuch earlier than another molecule of the same mass arrives at thesecond face 141 b. By plotting signal against mass, the differences inpositions on the horizontal axes are eliminated (, and the twoindependent measurements can be aligned for comparison and analysis. Onthe graphs of FIG. 2A and FIG. 2B using mass axes 210 a, 210 b,respectively, the linear spectrum 240 can be compared directly with thereflector spectrum 250.

[0052] The spectra 240, 250 are similar in some respects and differentin some respects. Several peaks are evident in both spectra 240, 250. Apeak represents a mass that is present in great numbers compared to mostmasses resolved by the spectrometer. For example peaks 242 a, 242 b, 242c and 242 c are evident in linear spectrum 240. Corresponding peaks, atthe same masses, in the reflector spectrum 250 include peaks 252 a, 252b, 252 c, 252 d, respectively.

[0053] The reflector spectrum 250, with the longer path and flighttimes, has greater resolution in mass, i.e., distinguishes smallerdifferences in mass, than does the linear spectrum 240. This is evidentby the narrowness of the peak 252 a in the reflector spectrum 250compared to the corresponding peak 242 a in the linear spectrum 240.

[0054] The reflector spectrum 250 suffers from fragmentation of largermolecules. This is illustrated by the relatively low signal levelassociated with peak 252 d at mass over 8000 amu compared to peak 252 aat mass less than 2000 amu in the reflector spectrum 250. In the linearspectrum 240, in contrast, the peak 242 d at mass over 8000 amu has agreater signal level than the peak 242 a under 2000 amu. Similarly, asmall peak near 9800 amu in linear spectrum 240 is completely missingfrom reflector spectrum 250.

[0055] Some masses that appear significant in one spectrum do not appearsignificant in the other. For example, the peak 242 b apparent in linearspectrum 240 at about 3000 amu appears in reflector spectrum 250 as arather insignificant peak 252 b. It is assumed, for purposes ofillustration, that a component of an agent of interest is associatedwith a peak at 3000 amu. The peak 242 b might be due to noise, since thepeak does not appear significant in the reflector spectrum 250. If thepeak 242 is due to noise, a conclusion that the agent is presentconstitutes a false alarm, which would seriously degrade the usefulnessof the system.

[0056] On the other hand, peaks that appear in both spectra allowdetections to be made with more confidence. It is assumed, for purposesof illustration, that a second agent of interest is associated withmultiple peaks at about 1800 amu, 4200 amu and 8500 amu. Peaks at thesemasses are observed in both spectra—peaks 242 a, 242 c, 242 d in linearspectrum 240 and peaks 252 a, 252 c, 252 d in reflector spectrum 250. Itis unlikely all three peaks are generated by noise in both spectra. Aconclusion that the second agent is present is justified. Such aconclusion is reached with some confidence based on a single ion beamformed from a single sample ionized in the source region, whichsimultaneously (e.g., from the same sample prepared once and insertedonce into the spectrometer) produced both spectra 240, 250.

[0057] The graphs of FIG. 2A and FIG. 2B illustrate that detection ofagents of interest in a sample are based, at least in part, on both thelinear spectrum 240 and the reflector spectrum 250 determined from thesignals output by detectors on both faces 141 a and 141 bsimultaneously.

[0058] The spectrum of FIG. 2A represents extra signal strength andindependent observations that are lost in conventional reflectedtime-of-flight mass spectrometers

[0059] 4. Method of Determining Complex Molecular Agents

[0060]FIG. 3 is a flow chart that illustrates at a high level a method300 for determining an agent in a mass spectrometer, according to anembodiment.

[0061] In step 310, an ion beam is formed from a sample in a sourceregion of a vacuum chamber. Any method known in the art for forming anion beam may be employed. In one embodiment, a laser beam is directed onthe sample in the source region 110 through a transparent portion of awall of the reflector region portion 124, and through the center hole148 in detector 140. The laser beam ionizes molecules in the sample. Anelectric field is applied in the source region portion 110 to acceleratethe molecules to a predetermined energy and to focus the ions into anion beam 102. Any method known in the art when the mass spectrometer isconstructed may be used to accelerate and focus the ion beam. The ionbeam is directed into the drift region portion 122 of the flight tube120.

[0062] In step 320, a linear signal is generated. The linear signal isrelated to the number of ions that impinge on detectors on a face of theplate that faces the source region during each of several timeintervals. For example, a signal is generated on linear output terminal142 based on the amount of ions of the diverging ion beam 102 thatstrike face 141 a of the dual-sided channelplate detector 140 every fewmicroseconds for several milliseconds. This signal is based on ions thatdo not pass through the hole 148 into the reflector region portion 124of the flight tube 120. Thus this signal represents extra signalstrength that is lost in a conventional reflector mass spectrometer.

[0063] In step 330, a reflector signal is generated. The reflectorsignal is related to the number of ions striking detectors on a face ofthe plate that faces the reflector region during each of several timeintervals. For example, a signal is generated on reflector outputterminal 144 based on the amount of ions of the reflecting ion beam 104that strike face 141 b of the dual-sided channelplate detector 140 everyfew microseconds for several milliseconds.

[0064] In step 340, a linear time-of-flight mass distribution isdetermined based on the linear signal. For example, a computer receivesthe linear signal and generates linear spectrum 240 based on the linearsignal according to instructions stored on the computer. This spectrumis based on observations of ions that are not measured in a conventionalreflector mass spectrometer. Thus this spectrum is a statisticallyindependent observation that is not available from a conventionalreflector mass spectrometer

[0065] In step 350, a reflector time-of-flight mass distribution isdetermined based on the reflector signal. For example, a computerreceives the reflector signal and generates reflector spectrum 250 basedon the reflector signal according to instructions stored on thecomputer.

[0066] In step 360, it is determined whether a particular agent ispresent in the sample based at least in part on the linear massdistribution and the reflected mass distribution. For example, acomputer determines whether a particular agent is present in the samplebased on the linear spectrum 240 and reflector spectrum 250 according toinstructions stored on the computer. In a conventional reflector massspectrometer, such a determination cannot be made with the sameconfidence due to measurement noise and fragmentation.

[0067] 5. Computer Implementation Overview

[0068]FIG. 4 is a block diagram that illustrates a computer system 400upon which an embodiment of the invention may be implemented. Computersystem 400 includes a communication mechanism such as a bus 410 forpassing information between other internal and external components ofthe computer system 400. Information is represented as physical signalsof a measurable phenomenon, typically electric voltages, but including,in other embodiments, such phenomena as magnetic, electromagnetic,pressure, chemical, molecular and atomic interactions. For example,north and south magnetic fields, or a zero and non-zero electricvoltage, represent two states (0, 1) of a binary digit (bit). A sequenceof binary digits constitutes digital data that is used to represent anumber or code for a character. A bus 410 includes many parallelconductors of information so that information is transferred quicklyamong devices coupled to the bus 410. One or more processors 402 forprocessing information are coupled with the bus 410. A processor 402performs a set of operations on information. The set of operationsinclude bringing information in from the bus 410 and placing informationon the bus 410. The set of operations also typically include comparingtwo or more units of information, shifting positions of units ofinformation, and combining two or more units of information, such as byaddition or multiplication. A sequence of operations to be executed bythe processor 402 constitute computer instructions.

[0069] Computer system 400 also includes a memory 404 coupled to bus410. The memory 404, such as a random access memory (RAM) or otherdynamic storage device, stores information including computerinstructions. Dynamic memory allows information stored therein to bechanged by the computer system 400. RAM allows a unit of informationstored at a location called a memory address to be stored and retrievedindependently of information at neighboring addresses. The memory 404 isalso used by the processor 402 to store temporary values duringexecution of computer instructions. The computer system 400 alsoincludes a read only memory (ROM) 406 or other static storage devicecoupled to the bus 410 for storing static information, includinginstructions, that is not changed by the computer system 400. Alsocoupled to bus 410 is a non-volatile (persistent) storage device 408,such as a magnetic disk or optical disk, for storing information,including instructions, that persists even when the computer system 400is turned off or otherwise loses power.

[0070] Information, including instructions, is provided to the bus 410for use by the processor from an external input device 412, such as akeyboard containing alphanumeric keys operated by a human user, or asensor. A sensor detects conditions in its vicinity and transforms thosedetections into signals compatible with the signals used to representinformation in computer system 400. Other external devices coupled tobus 410, used primarily for interacting with humans, include a displaydevice 414, such as a cathode ray tube (CRT) or a liquid crystal display(LCD), for presenting images, and a pointing device 416, such as a mouseor a trackball or cursor direction keys, for controlling a position of asmall cursor image presented on the display 414 and issuing commandsassociated with graphical elements presented on the display 414.

[0071] In the illustrated embodiment, special purpose hardware, such asan application specific integrated circuit (IC) 420, is coupled to bus410. The special purpose hardware is configured to perform operationsnot performed by processor 402 quickly enough for special purposes.Examples of application specific ICs include graphics accelerator cardsfor generating images for display 414, cryptographic boards forencrypting and decrypting messages sent over a network, speechrecognition, and interfaces to special external devices, such as roboticarms and medical scanning equipment that repeatedly perform some complexsequence of operations that are more efficiently implemented inhardware.

[0072] Computer system 400 also includes one or more instances of acommunications interface 470 coupled to bus 410. Communication interface470 provides a two-way communication coupling to a variety of externaldevices that operate with their own processors, such as printers,scanners and external disks. In general the coupling is with a networklink 478 that is connected to a local network 480 to which a variety ofexternal devices with their own processors are connected. For example,communication interface 470 may be a parallel port or a serial port or auniversal serial bus (USB) port on a personal computer. In someembodiments, communications interface 470 is an integrated servicesdigital network (ISDN) card or a digital subscriber line (DSL) card or atelephone modem that provides an information communication connection toa corresponding type of telephone line. In some embodiments, acommunication interface 470 is a cable modem that converts signals onbus 410 into signals for a communication connection over a coaxial cableor into optical signals for a communication connection over a fiberoptic cable. As another example, communications interface 470 may be alocal area network (LAN) card to provide a data communication connectionto a compatible LAN, such as Ethernet. Wireless links may also beimplemented. For wireless links, the communications interface 470 sendsand receives electrical, acoustic or electromagnetic signals, includinginfrared and optical signals, that carry information streams, such asdigital data. Such signals are examples of carrier waves.

[0073] The term computer-readable medium is used herein to refer to anymedium that participates in providing instructions to processor 402 forexecution. Such a medium may take many forms, including, but not limitedto, non-volatile media, volatile media and transmission media.Non-volatile media include, for example, optical or magnetic disks, suchas storage device 408. Volatile media include, for example, dynamicmemory 404. Transmission media include, for example, coaxial cables,copper wire, fiber optic cables, and waves that travel through spacewithout wires or cables, such as acoustic waves and electromagneticwaves, including radio, optical and infrared waves. Signals that aretransmitted over transmission media are herein called carrier waves.

[0074] Common forms of computer-readable media include, for example, afloppy disk, a flexible disk, a hard disk, a magnetic tape, or any othermagnetic medium, a compact disk ROM (CD-ROM), or any other opticalmedium, punch cards, paper tape, or any other physical medium withpatterns of holes, a RAM, a programmable ROM (PROM), an erasable PROM(EPROM), a FLASH-EPROM, or any other memory chip or cartridge, a carrierwave, or any other medium from which a computer can read.

[0075] Network link 478 typically provides information communicationthrough one or more networks to other devices that use or process theinformation. For example, network link 478 may provide a connectionthrough local network 480 to a host computer 482 or to equipment 484operated by an Internet Service Provider (ISP). ISP equipment 484 inturn provides data communication services through the public, world-widepacket-switching communication network of networks now commonly referredto as the Internet 490. A computer called a server 492 connected to theInternet provides a service in response to information received over theInternet. For example, server 492 provides information representingvideo data for presentation at display 414.

[0076] The invention is related to the use of computer system 400 forimplementing the techniques described herein. According to oneembodiment of the invention, those techniques are performed by computersystem 400 in response to processor 402 executing one or more sequencesof one or more instructions contained in memory 404. Such instructions,also called software and program code, may be read into memory 404 fromanother computer-readable medium such as storage device 408. Executionof the sequences of instructions contained in memory 404 causesprocessor 402 to perform the method steps described herein. Inalternative embodiments, hardware, such as application specificintegrated circuit 420, may be used in place of or in combination withsoftware to implement the invention. Thus, embodiments of the inventionare not limited to any specific combination of hardware and software.

[0077] The signals transmitted over network link 478 and other networksthrough communications interface 470, which carry information to andfrom computer system 400, are exemplary forms of carrier waves. Computersystem 400 can send and receive information, including program code,through the networks 480, 490 among others, through network link 478 andcommunications interface 470. In an example using the Internet 490, aserver 492 transmits program code for a particular application,requested by a message sent from computer 400, through Internet 490, ISPequipment 484, local network 480 and communications interface 470. Thereceived code may be executed by processor 402 as it is received, or maybe stored in storage device 408 or other non-volatile storage for laterexecution, or both. In this manner, computer system 400 may obtainapplication program code in the form of a carrier wave.

[0078] Various forms of computer readable media may be involved incarrying one or more sequence of instructions or data or both toprocessor 402 for execution. For example, instructions and data mayinitially be carried on a magnetic disk of a remote computer such ashost 482. The remote computer loads the instructions and data into itsdynamic memory and sends the instructions and data over a telephone lineusing a modem. A modem local to the computer system 400 receives theinstructions and data on a telephone line and uses an infra-redtransmitter to convert the instructions and data to an infra-red signal,a carrier wave serving as the network link 478. An infrared detectorserving as communications interface 470 receives the instructions anddata carried in the infrared signal and places information representingthe instructions and data onto bus 410. Bus 410 carries the informationto memory 404 from which processor 402 retrieves and executes theinstructions using some of the data sent with the instructions. Theinstructions and data received in memory 404 may optionally be stored onstorage device 408, either before or after execution by the processor402.

[0079] 6. Extensions and Alternatives

[0080] In the foregoing specification, the invention has been describedwith reference to specific embodiments thereof. It will, however, beevident that various modifications and changes may be made theretowithout departing from the broader spirit and scope of the invention.The specification and drawings are, accordingly, to be regarded in anillustrative rather than a restrictive sense.

What is claimed is:
 1. An apparatus for simultaneously detecting directand reflected ions in a mass spectrometer, comprising: a flight tube; asource for generating an ion beam of ions of a sample and introducingthe ion beam into a first portion of the flight tube; a reflector forreflecting ions from the ion beam in a second portion of the flighttube; and a plate substantially perpendicular to an axis of the ionbeam, wherein the plate is disposed between the first portion oftheflight tube and the second portion of the flight tube, the plate hasa hole through which some ions in the ion beam may pass from the firstportion to the second portion of the flight tube, and each of twoopposite faces of the plate includes a set of one or more ion detectors.2. The apparatus as recited in claim 1, further comprising: a firstsignal terminal for carrying a first signal based on ions in the ionbeam detected by a first set of one or more ion detectors during a timeinterval, the first set on a first face of the two opposite faces, thefirst face forming a side of the first portion of the flight tube; and asecond signal terminal for carrying a second signal based on ions in theion beam detected by a second set of one or more ion detectors duringthe time interval, the second set on a second face of the two oppositefaces, the second face forming a side of the second portion of theflight tube.
 3. The apparatus as recited in claim 1, wherein the set ofion detectors is a plurality of microchannel plate ion detectors.
 4. Theapparatus as recited in claim 1, wherein a direct line, time-of-flightmass spectrum determination is based on ions detected by a first set ofone or more ion detectors on a first face of the two opposite faces, thefirst face directed towards the first portion of the flight tube.
 5. Theapparatus as recited in claim 1, wherein a reflected time-of-flight massspectrum determination is based on ions detected by a second set of oneor more ion detectors on a second face of the two opposite faces, thesecond face directed towards the second portion of the flight tube. 6.The apparatus as recited in claim 1, wherein the plate separates thefirst portion from the second portion of the flight tube.
 7. A methodfor fabricating an apparatus for simultaneously detecting direct andreflected ions in a mass spectrometer, comprising: installing, onto aflight tube, a source for generating an ion beam of ions of a sample andintroducing the ion beam into a first portion of the flight tube;installing, in the flight tube, a reflector for reflecting ions from theion beam in a second portion of the flight tube; and installing, in theflight tube, between the first portion of the flight tube and the secondportion of the flight tube, a plate substantially perpendicular to anaxis of the ion beam, wherein the plate has a hole through which someions in the ion beam may pass from the first portion to the secondportion of the flight tube, and each of two opposite faces of the plateincludes a set of one or more ion detectors.
 8. A method forsimultaneously detecting direct and reflected ions in a massspectrometer, comprising: forming, in a source of ions, a ion beam froma sample; generating a first signal indicating a number of first ionsfrom the ion beam, the first ions striking a first face of a platedirected toward the source of ions; generating a second signalindicating a number of second ions from the same ion beam, the secondions striking a second face of the plate, the second face directed awayfrom the source of ions and directed toward the second ions that passthrough a hole in the plate and that are reflected in a reflectingelectric field; determining a direct time-of-flight mass distributionbased on the first signal; and determining a reflected time-of-flightmass distribution based on the second signal.
 9. A method as recited inclaim 8, wherein the first signal indicates a number of the first ionsin each time interval of multiple time intervals.
 10. A method asrecited in claim 8, wherein the second signal indicates a number of thesecond ions in each time interval of multiple time intervals.
 11. Amethod as recited in claim 8, further comprising determining whether aparticular agent is present in the sample based, at least in part, onthe direct time-of-flight mass distribution and the reflectedtime-of-flight mass distribution.
 12. A method for determining whether aparticular agent is present in a sample, comprising: receiving a firstsignal indicating a number of first ions from a ion beam generated fromthe sample in a source, the first ions striking a first face of a platedirected toward a source of ions; receiving a second signal indicating anumber of second ions from the same ion beam, the second ions striking asecond face of the plate, the second face directed away from the sourceof ions and directed toward the second ions that pass through a hole inthe plate and that are reflected in a reflecting electric field;determining a direct time-of-flight mass distribution based on the firstsignal; determining a reflected time-of-flight mass distribution basedon the second signal; and determining whether the particular agent ispresent in the sample based, at least in part, on the directtime-of-flight mass distribution and the reflected time-of-flight massdistribution.
 13. A computer-readable medium carrying one or moresequences of instructions for determining whether a particular agent ispresent in a sample, wherein execution of the one or more sequences ofinstructions by one or more processors causes the one or more processorsto perform the steps: receiving a first signal indicating a number offirst ions from a ion beam generated from the sample in a source, thefirst ions striking a first face of a plate directed toward a source ofions; receiving a second signal indicating a number of second ions fromthe same ion beam, the second ions striking a second face of the plate,the second face directed away from the source of ions and directedtoward the second ions that pass through a hole in the plate and thatare reflected in a reflecting electric field; determining a directtime-of-flight mass distribution based on the first signal; determininga reflected time-of-flight mass distribution based on the second signal;and determining whether the particular agent is present in the samplebased, at least in part, on the direct time-of-flight mass distributionand the reflected time-of-flight mass distribution.
 14. An apparatus fordetermining whether a particular agent is present in a sample,comprising: a processor; and a computer readable medium carrying one ormore sequences of instructions, wherein execution of the one or moresequences of instructions by the processor causes the processor toperform the steps of: receiving a first signal indicating a number offirst ions from a ion beam generated from the sample in a source, thefirst ions striking a first face of a plate directed toward a source ofions; receiving a second signal indicating a number of second ions fromthe same ion beam, the second ions striking a second face of the plate,the second face directed away from the source of ions and directedtoward the second ions that pass through a hole in the plate and thatare reflected in a reflecting electric field; determining a directtime-of-flight mass distribution based on the first signal; determininga reflected time-of-flight mass distribution based on the second signal;and determining whether the particular agent is present in the samplebased, at least in part, on the direct time-of-flight mass distributionand the reflected time-of-flight mass distribution.